The observed prevalence of an HR deficiency footprint in advanced chordomas, which is reminiscent of the genomic features of breast, ovarian, and prostate cancer in which HR deficiency has emerged as a therapeutic liability15,19, provides a rationale for genomics-guided therapy using agents, either alone or in combination, that are preferentially toxic to HR-incompetent cells, such as PARP inhibitors, platinum derivatives, or trabectedin. This evidence concerns the gene PARP1 and Familial prostate cancer.